Avoiding the Fatal Flaw: How Nicotine Pouch PMTAs Can Stay Ahead of FDA’s Next Move?

When FDA deployed the “fatal flaw” concept during ENDS PMTA reviews, it was seen by many as a subjective screen built on guidance rather than regulation. Under section IV.D of the ENDS guidance, applicants were guided to consider changes in use patterns, including switching, initiation, dual use, and cessation, when demonstrating that marketing a new tobacco product would be appropriate for the protection of public health. The guidance did not specify the studies required to provide this evidence. FDA interpreted the absence of specific evidence, particularly studies supporting adult switching benefits, as a reason to conclude that the potential benefit to smokers did not outweigh the risk to youth. That interpretation became the basis for rapid denials and led to several legal challenges.

Now, the landscape is different. The PMTA Final Rule has been in place since November 2021, setting specific requirements, including specific content and format requirements for applications. This raises an important question: With mounting pressure to clear the backlog of oral nicotine pouch and other oral product PMTAs, could FDA move from the more subjective fatal flaw approach previously used for ENDS to an objective one, using explicit elements of the rule as grounds to refuse to accept or refuse to file incomplete applications? If so, the implications for both legacy and new submissions are significant.

What FDA Has Said: The Pilot and the PMTA Final Rule

On 18 September 2025, FDA’s Center for Tobacco Products launched a pilot to streamline nicotine pouch PMTA reviews. The agency says it will focus on the “most critical elements” for this product category, increase real-time communication, and aim for shorter review timelines, explicitly situating pouches lower on the “continuum of risk” than combusted products. FDA also flagged rising accidental pediatric exposures, urging child-resistant packaging, a signal that packaging and human-factors mitigations will be watched closely.

Separately, the PMTA Final Rule (2021) specifies the content and format FDA expects, and the procedures it follows during review (21 CFR Part 1114). The rule anchors the review against the statutory “appropriate for the protection of public health” standard and heavily emphasizes product characterization, manufacturing methods and controls, consistency, and other data sufficient for FDA to complete a substantive scientific review. For any PMTA, the rule outlines the application's minimum requirements. If a PMTA does not contain the required information in sufficient detail, FDA can refuse to file, refuse to accept, or deny after a rapid substantive screen.

There is also public reporting that, inside the pilot, FDA may rely more on category-level literature for specific questions (for example, switching or reduction outcomes) rather than demanding a full suite of product-specific studies in every area. However, the agency’s newsroom post stops short of confirming that point. If borne out, the trade-off will be increased pressure on other critical elements such as manufacturing quality, product specifications, packaging, and toxicology to carry more of the evidentiary load.

Why a Fatal-Flaw Screen for Pouches Is More Likely Now

• Legal cover

When FDA applied the fatal flaw approach to ENDS, some courts ruled that the agency acted unlawfully because it appeared to require at least one of two specific study types (longitudinal cohort studies and randomized controlled trials) without clearly stating that these were mandatory in advance. The Fifth Circuit even described this as a “surprise switcheroo,” arguing that FDA had shifted from guidance (which allowed flexibility) to rigid evidentiary demands after applications were submitted. However, the Supreme Court later upheld FDA’s authority to deny ENDS PMTAs, provided the agency applies published standards consistently. For nicotine pouches, the situation is very different. The PMTA Final Rule has been in place since late 2021, before most pouch applications were filed. It sets out explicit content and format requirements, giving FDA a clear legal foundation to refuse to accept or refuse to file applications that omit critical elements. This makes future legal challenges significantly harder.

• Operational pressure

FDA faces a large backlog of pouch PMTAs. To address this, it launched a pilot focused on “critical elements,” signaling a move toward a checklist approach that are defined by the PMTA rule requirement. Missing key items could mean an application never reaches full scientific review, which could result in rapid assessments and determinations when combined with the FDA’s Elsa AI tool.

• Industry pressure

Many companies that have invested heavily in robust, data-rich PMTAs are lobbying FDA to clear the backlog. They want a level playing field, and that starts with removing applications submitted with minimal information or STN-only applications from review. This behind-the-scenes pressure is adding momentum for FDA to accelerate and tighten its filing review process so that time and resources go toward the applications that have enough information for full scientific review.

Reading Between the Lines: The Broughton View

If FDA seeks to reduce the number of pending pouch PMTAs (including those submitted for Submission Tracking Number (STN) only filings with minimal information that would not survive a filing review based on the PMTA rule here is where a fatal-flaw-style screen could land first:

• Product characterization and specifications
  Complete description of compositions (nicotine form and level, pH, ingredients, nicotine release profile [dissolution]), HPHC yields, and statistical lot-to-lot variability sufficient to support manufacturing consistency.
• Manufacturing methods, facilities, and controls (CGMP-like detail)
  The Tobacco Control Act and PMTA rule requires FDA to consider the methods, facilities, and controls used to manufacture, process, and pack the product. Expect FDA to scrutinize process controls closely that support the quality and consistency of manufactured products, noting any deviations could make a product a “new tobacco product” requiring authorization before marketing.
• Shelf-life (stability) data
  While not headlined in FDA’s pilot announcement, the PMTA rule’s focus on consistent product performance implies that stability over labelled shelf life (such as nicotine content, degradation products, microbial content, and packaging interaction) is integral to characterization and manufacturing controls. The final rule clearly states that applications must contain stability data assessed at the beginning (zero time), middle, and end of the expected shelf life.
• Toxicology and abuse liability
  For pouches, FDA has already emphasized the continuum of risk and lower toxicant exposure versus combustibles. However, triage denials could still flow from missing core toxicology (for example, extractables or leachables where warranted, in vitro data, ingredient risk assessments) or abuse liability assessments that underpin the population health modelling.
• Packaging, labelling, and youth-risk mitigations
  With FDA publicly highlighting child-resistant packaging (CRP) amidst rising pediatric exposures, applications without a risk mitigation, such as CRP evidence, clear warnings, and tamper-evidence will likely face quick negative outcomes. Human-factors rationales tied to accidental exposures and youth appeal are likely to be treated as critical.
• Evidence sufficiency strategy and behavioral considerations
  If FDA really does relax certain product-specific outcomes studies under the pilot (per Reuters’ transcript reporting), sponsors will need to connect category-level evidence to their product via analytical comparators, release profiles, and labelled use conditions. Failure to make a credible bridging argument renders the provided literature data unsuitable for the application.

Although youth usage rates for pouches are currently low, the Tobacco Control Act still requires FDA to weigh risks and benefits to the population as a whole, including users and non-users. This means considering whether marketing the product increases or decreases the likelihood of existing tobacco users quitting and whether non-users will start. The burden of proof on switching and perceptions may not be as heavy as for ENDS, but it does not disappear. Sponsors may rely on literature or truncated studies, yet these must be relevant to the product and clearly linked to the APPH standard. Importantly, if youth uptake trends change, FDA could tighten expectations quickly. Addressing these behavioral elements now can create a more robust long-term strategy.

Implications for Legacy and STN-Only Applications

Applications submitted with minimal scientific content, such as placeholder filings intended only to secure an STN, are especially at risk. Under the PMTA Final Rule, FDA can refuse to file or deny any application that lacks the core information needed to determine whether marketing the product is appropriate for the protection of public health. If FDA follows the ENDS precedent and aims to significantly reduce the backlog, these incomplete applications could be the first to go. Those missing critical data or even a clear plan to provide it are likely to be treated as low-hanging fruit.

Action

If you are preparing or updating a nicotine pouch or other oral product PMTA, now is the time to act. Review your application against the PMTA Final Rule, identify gaps in product characterization, stability, packaging, and behavioral evidence, and close them before FDA does it for you. Developing a proactive strategy now could be the difference between a Marketing Granted Order today and a rapid denial tomorrow.

Contact Broughton to discuss how we can help you strengthen your PMTA strategy, close critical gaps, and position your product for success.